1. Field of the Invention
The present invention relates to processes for spinning polypeptide fibers. More particularly, the invention involves forming polypeptide fibers by dissolving a polypeptide in a solvent system comprising lithium thiocyanate (LiSCN), and a liquefied phenol selected from the group consisting of phenol, m-chlorophenol, m-fluorophenol, and m-bromophenol or mixtures thereof and extruding the solution to form fibers. The process of the current invention is especially useful for spinning fibers from silk fibroin solutions.
2. Description of the Related Art
Proteins are complex, high molecular weight polymers containing carbon, hydrogen, nitrogen, oxygen, and usually sulfur. These protein macromolecules, or polypeptides, are comprised of amino acid residues which are linked together by peptide bonds, (--CO--NH--). Proteins which are found in nature have a wide range of properties depending on their particular amino acid sequence and generally fall into three categories: structural, regulatory, and catalytic. Certain naturally occurring structural polypeptides have fibrous structures including keratin, silk, elastin, and collagen. Structural polypeptides may also be synthesized by either recombinant DNA or, in some cases, by classical organic synthetic methods. Potential applications for structural polypeptide fibers include synthetic or simulated food, textiles, hard and soft tissue prostheses, artificial ligaments, and tough composite materials.
Polypeptides do not melt because of a high degree of hydrogen bonding, thus they require solubilization in a solvent for processing into useful articles.
It is known in the art that fiber spinnable polypeptide solutions may be prepared by dissolving a polypeptide in strongly acidic solvents, such as trichloroacetic acid or trifluoroacetic acid. Organic solvents may also be used as described in Ballard et al., U.S. Pat. No., 3,121,766. This reference discloses wet spinning polypeptide fibers from a birefringent solution of poly-gamma-methyl glutamate in mixed organic solvents such as methylene chloride/ethyl acetate. Acetone, ethyl acetate, and a mixture of these compounds are described as suitable coagulating fluids.
Bamford and Hanby, U.S. Pat. No., 2,697,085 and British published Specification 675,299 disclose wet and dry spinning fibers from a solution containing anhydrocarboxy-amino-acids in a solvent comprising a major proportion of a monohydric phenol, a lower aliphatic carboxylic acid, a halogen-substituted lower aliphatic acid, or a mixture of these compounds. Hydroxyl-containing compounds such as water, methyl alcohol, and ethyl alcohol are described as suitable coagulating fluids.
Ryoichi, U.S. Pat. No., 3,387,070, discloses a process for producing shaped articles of water-insoluble poly-DL-alanine. This method involves dissolving poly-DL-alanine in a mixture consisting of more than 40% by volume of at least one phenol, 0.5-60% by volume of acids having a pKa below 5.0 to produce a polymer solution, and extruding the solution into a coagulating bath.
A particularly important naturally occurring polypeptide is silk fibroin (silkworm silk) which occurs in fibrous form having high strength and a soft hand. The nature of silk fibroin makes it suitable for a wide range of uses including textile applications and in suture materials. However, one problem with obtaining silk from silkworms is that they produce filaments in only one size (ca. 1 denier). Thus, twisted or braided yarns must be used when loads exceed a few grams. Unfortunately, the interstices of such a multifilament yarn can be a route for infection. Accordingly, it would be desirable to be able to produce silk fibers in deniers other than those found in nature. These fibers would be suitable for such applications as monofilament sutures. An object of this invention is to produce such fibers.
Fibroin is known to be soluble in certain high ionic strength aqueous salt solutions, for example, aqueous lithium thiocyanate (LiSCN), sodium thiocyanate (NaSCN), calcium thiocyanate (Ca(SCN).sub.2), magnesium thiocyanate (Mg(SCN).sub.2), calcium chloride (CaCl.sub.2), lithium bromide (LiBr), zinc chloride (ZnCl.sub.2), magnesium chloride (MgCl.sub.2), and copper salts, such as copper nitrate (Cu(NO.sub.3).sub.2), copper ethylene diamine (Cu(NH.sub.2 CH.sub.2 CH.sub.2 NH.sub.2).sub.2 (OH).sub.2), and Cu(NH.sub.3).sub.4 (OH).sub.2. It has long been known that the salts can be dialyzed out of such aqueous salt/fibroin solutions to produce aqueous solutions of fibroin which are similar in some ways to the liquid contents of a silkworm's silk gland. Fibers have been spun from aqueous fibroin solutions of this type, but more commonly, the solutions have been used to cast films for structure studies. Those skilled in the art have attempted to find suitable solvents for preparing silk fibroin solutions which may be subsequently spun into fibers.
For example, Otoi et al., Japanese Kokoku Patent No. SHO 57[1982]-4723 describe a method for preparing a silk spinning solution involving dissolution of fibroin in an aqueous solution of copper-ethylenediamine, copper hydroxide-ammonia, copper hydroxide-alkali-glycerin, lithium bromide, sodium thiocyanate, or nitrates or thiocyanates of zinc, calcium, or magnesium. The solution is then dialyzed using a multilayered structure and used to fabricate fibers or films.
Although polypeptide fibers have been spun from the spinning solutions described above, one problem is that many of the solvents tend to be harsh and partially degrade the polypeptide. Dichloroacetic acid, trifluoroacetic acid, and a mixture of formic acid/lithium chloride, are especially harsh and subject the polymer to some degree of degradation. Fibers prepared from such solutions tend to be deficient in certain physical properties, such as mechanical strength. Therefore, there is a need to prepare a fiber spinnable polypeptide solution containing a solvent which does not measurably degrade the polypeptide. An object of the present invention is to prepare such a solution and to produce fibers therefrom.